Demanding proof that genetically modified foods
are safe is all very well, but without a rational system
for testing conventional foods, we may never get it

EARLIER this year, Britain was rocked by claims that genetically
modified
foods are dangerous. Arpad Pusztai, a biochemist who used to work
at the
Rowett Research Institute in Scotland, said he had shown that GM
potatoes
were harmful to rats because of their genetic modification alone.

Were the GM potatoes toxic? On the basis of Pusztai's evidence,
it's
impossible to say. In fact, his results support only one obvious
conclusion:
rats hate potatoes.

Pusztai fed separate groups of rats on normal or GM potatoes to
see if the
GM food had different effects. That's good, basic toxicology.
Unfortunately
he couldn't make the animals eat enough potato, so they were
malnourished
no matter which kind they were eating.

According to toxicologists who examined the data, changes in
their organ
weights and immune reactivity showed no unambiguous association
with
genetic modification (This Week, 6 March, p 13). Starvation or
known
toxins in raw potato were the most likely culprits for any
changes seen in
the rats.

These experiments reveal a serious problem that is only now being
grasped
by the biotechnology industry: standard toxicology tests don't
work for
food. It is often difficult to feed lab animals enough GM fodder,
whether or
not they find it palatable, to see if it has undesirable effects
compared with
unmodified food. Essentially, animal models are not sensitive
enough to
reveal small differences between modified and unmodified foods.

Nonstarter

Even if you manage to get animals to eat enough test food, you
risk
changing their diet so profoundly that even those eating
unmodified food
will be abnormal. For all but the most blatantly toxic GM foods,
this may
make it impossible to draw meaningful conclusions from such
experiments.

Politicians, taken aback by huge public mistrust of
"Frankenfoods", are also
realising that safety testing of these foods is not
straightforward. In Britain,
the Cabinet's biotechnology committee has commissioned a report
on the
human health implications of GM foods from the government's Chief
Medical Officer and Chief Scientific Adviser, due to be published
this
month. A Cabinet Office memo, leaked by Friends of the Earth,
asks: "Why
don't we require a pharmaceutical-type analysis of the safety of
these foods,
with proper trials?" But as the problems to date have shown,
the
proposition is a nonstarter.

So how can we check the safety of GM food? Scientists from the 29
industrialised countries of the OECD concluded at a meeting in
Paris in
December that a whole new approach is needed. In September, they
will
meet again to start drawing up ways of carrying out such checks.

They are up against some serious logistical problems. Harry
Kuiper of the
State Institute for Quality Control of Agricultural Products in
Wageningen,
Netherlands, tested a GM tomato by freeze-drying it and feeding
so much
to rats that each got the equivalent of 13 of fresh tomatoes a
day. Any
more, and they would have been poisoned by the basic nutrients,
such as
potassium, in the tomato powder.

"But toxicologists still said we hadn't fed them enough to
get a meaningful
result," says Kuiper. The usual approach for testing a new
food additive, for
instance, is to feed it to a rat until a toxic effect is
observed. That way, you
get an idea of the nature and threshold of any toxicity. But with
tomatoes,
the researchers never managed to reach that threshold. In
standard
toxicological terms, says Kuiper, they have not been adequately
tested.
Others would argue that if such large amounts are harmless, the
food
cannot reasonably be called toxic.

Nonetheless, these difficulties mean that GM food developers
usually avoid
testing whole foods. Instead, they try to isolate the changed
portion and test
that. As an example, Roy Fuchs, head of scientific affairs at
Monsanto, one
of the world's biggest developers of GM food, quotes potatoes
carrying a
gene for the Bt toxin, an insecticide normally produced by
Bacillus
thuringensis. Monsanto sells its Bt potatoes in the US and is
applying for a
European licence. Fuchs says that the potatoes, like all
genetically
engineered plants so far, do not produce enough of the product of
the novel
gene for it to be isolated from the plants themselves and tested.
"So we put
the novel genes in bacteria, produce the gene product and test it
by
conventional methods." However, the protein made by the
bacteria may
not be the same as that made by the plant, especially in its
potential to cause
allergy.

The production of a novel protein is only one of the potentially
harmful
changes that occur in when a foreign gene is inserted into a
plant. Because
the positioning of the novel gene within the plant's DNA is
essentially
random, it may alter the plant's expression of its own
genes--with
unpredictable effects. It is this kind of change that stymies
conventional
toxicology. Food is a complex mixture of substances that occur in
different
quantities in different varieties of crops and in the same
variety grown
under even slightly different conditions. When is a change in one
or several
of those substances a problem?

Unfortunately, says Peter Kearns of the OECD in Paris, no one has
ever
tested conventional food for toxicity, so no one quite knows
where to start.
One exception is potatoes. Conventional plant breeders in the US
and the
Netherlands test new potato varieties for elevated levels of
known toxins
such as solenines. French breeders do not--and there are no legal
requirements in any country to do so. And that still leaves
toxins in GM
foods that we may not yet know about. "We have to think
through these
things case by case," says Kearns, starting with a better
understanding of
what is in normal crops.

Kuiper's institute is working on a screening test that detects
differences in
the pattern of messenger RNA molecules produced by normal and
transgenic tomatoes. The hope it that this will provide a fast
way to see if
there have been large changes in gene expression. The method can
reliably
detect differences between red and green tomatoes--which is
encouraging,
says Kuiper, because green ones produce more toxins.

Key differences

The team has also compared the chemicals synthesised by normal
and
transgenic plants by looking at their nuclear magnetic resonance
(NMR)
spectra. Nearly every chemical compound in the plant produces a
characteristic "fingerprint" of peaks. The screening
test revealed that there
were up to eightfold differences in concentrations of sugars,
amino acids
and various unidentified compounds. Impressive as this sounds, it
may not
be significant: Kuiper notes that there were greater differences
between
unaltered tomatoes grown in different conditions than there were
between
GM and normal tomatoes grown in identical conditions.

A better way of exploiting NMR might be to use it to find
substances that
differ in transgenic foods and then to test these substances in,
for example,
cell cultures, to see if the changes could be harmful. The need
for such tests
may be soon be pressing. But when crops are engineered to produce
a
number of desired nutrients or "nutraceuticals",
changes in the plant's own
gene expression could become much more complex and their
potentially
toxic effects harder to test.

However, proponents of GM foods point out that whichever
direction food
testing goes, the subtly altered products on our plates will have
been tested
far more thoroughly than any conventional food. After all, even
ordinary
kidney beans are poisonous if undercooked. Dozens of people die
each year
from cyanide from peach seeds. Manioc, the staple diet of
millions, had to
be grated, squeezed and cooked to drive off the cyanide before
improved
varieties became available. And some of the most notorious
food-linked
poisons, such as aflatoxins in grain, do not come from the food
but moulds
that infect it. In the comparison between modified and unmodified
foods,
nothing is clear cut. And testing is never simple. Debora
MacKenzie